Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1983 Nov 1;97(5):1321–1326. doi: 10.1083/jcb.97.5.1321

Nuclear RNA-protein interactions and messenger RNA processing

PMCID: PMC2112690  PMID: 6355116

Abstract

Eucaryotic messenger RNA precursors are processed in nuclear ribonucleoprotein particles (hnRNP). Here recent work on the structure of hnRNP is reviewed, with emphasis on function. Detailed analysis of a specific case, the altered assembly of hnRNP in heat-shocked Drosophila and mammalian cells, leads to a general hypothesis linking hnRNP structure and messenger RNA processing.

Full Text

The Full Text of this article is available as a PDF (874.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adesnik M., Darnell J. E. Biogenesis and characterization of histone messenger RNA in HeLa cells. J Mol Biol. 1972 Jun 28;67(3):397–406. doi: 10.1016/0022-2836(72)90458-5. [DOI] [PubMed] [Google Scholar]
  2. Ashburner M., Bonner J. J. The induction of gene activity in drosophilia by heat shock. Cell. 1979 Jun;17(2):241–254. doi: 10.1016/0092-8674(79)90150-8. [DOI] [PubMed] [Google Scholar]
  3. Berg O. G., Winter R. B., von Hippel P. H. Diffusion-driven mechanisms of protein translocation on nucleic acids. 1. Models and theory. Biochemistry. 1981 Nov 24;20(24):6929–6948. doi: 10.1021/bi00527a028. [DOI] [PubMed] [Google Scholar]
  4. Beyer A. L., Bouton A. H., Hodge L. D., Miller O. L., Jr Visualization of the major late R strand transcription unit of adenovirus serotype 2. J Mol Biol. 1981 Apr 5;147(2):269–295. doi: 10.1016/0022-2836(81)90441-1. [DOI] [PubMed] [Google Scholar]
  5. Beyer A. L., Bouton A. H., Miller O. L., Jr Correlation of hnRNP structure and nascent transcript cleavage. Cell. 1981 Oct;26(2 Pt 2):155–165. doi: 10.1016/0092-8674(81)90299-3. [DOI] [PubMed] [Google Scholar]
  6. Beyer A. L., Christensen M. E., Walker B. W., LeStourgeon W. M. Identification and characterization of the packaging proteins of core 40S hnRNP particles. Cell. 1977 May;11(1):127–138. doi: 10.1016/0092-8674(77)90323-3. [DOI] [PubMed] [Google Scholar]
  7. Beyer A. L., Miller O. L., Jr, McKnight S. L. Ribonucleoprotein structure in nascent hnRNA is nonrandom and sequence-dependent. Cell. 1980 May;20(1):75–84. doi: 10.1016/0092-8674(80)90236-6. [DOI] [PubMed] [Google Scholar]
  8. Calvet J. P., Pederson T. Base-pairing interactions between small nuclear RNAs and nuclear RNA precursors as revealed by psoralen cross-linking in vivo. Cell. 1981 Nov;26(3 Pt 1):363–370. doi: 10.1016/0092-8674(81)90205-1. [DOI] [PubMed] [Google Scholar]
  9. Calvet J. P., Pederson T. Heterogeneous nuclear RNA double-stranded regions probed in living HeLa cells by crosslinking with the psoralen derivative aminomethyltrioxsalen. Proc Natl Acad Sci U S A. 1979 Feb;76(2):755–759. doi: 10.1073/pnas.76.2.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Calvet J. P., Pederson T. Nucleoprotein organization of inverted repeat DNA transcripts in heterogeneous nuclear RNA-ribonucleoprotein particles from HeLa cells. J Mol Biol. 1978 Jul 5;122(3):361–378. doi: 10.1016/0022-2836(78)90195-x. [DOI] [PubMed] [Google Scholar]
  11. Calvet J. P., Pederson T. Secondary structure of heterogeneous nuclear RNA: two classes of double-stranded RNA in native ribonucleoprotein. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3705–3709. doi: 10.1073/pnas.74.9.3705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Corces V., Holmgren R., Freund R., Morimoto R., Meselson M. Four heat shock proteins of Drosophila melanogaster coded within a 12-kilobase region in chromosome subdivision 67B. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5390–5393. doi: 10.1073/pnas.77.9.5390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Darnell J. E., Jr Variety in the level of gene control in eukaryotic cells. Nature. 1982 Jun 3;297(5865):365–371. doi: 10.1038/297365a0. [DOI] [PubMed] [Google Scholar]
  14. Economidis I. V., Pederson T. Assembly of nuclear ribonucleoprotein particles during in vitro transcription. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1469–1473. doi: 10.1073/pnas.79.5.1469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Economidis I. V., Pederson T. In vitro assembly of a pre-messenger ribonucleoprotein. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4296–4300. doi: 10.1073/pnas.80.14.4296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Economidis I. V., Pederson T. Structure of nuclear ribonucleoprotein: heterogeneous nuclear RNA is complexed with a major sextet of proteins in vivo. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1599–1602. doi: 10.1073/pnas.80.6.1599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Faiferman I., Hamilton M. G., Pogo A. O. Nucleoplasmic ribonucleoprotein particles of rat liver. I. Selective degradation by nuclear nucleases. Biochim Biophys Acta. 1970 Apr 15;204(2):550–563. doi: 10.1016/0005-2787(70)90175-9. [DOI] [PubMed] [Google Scholar]
  18. Findly R. C., Pederson T. Regulated transcription of the genes for actin and heat-shock proteins in cultured Drosophila cells. J Cell Biol. 1981 Feb;88(2):323–328. doi: 10.1083/jcb.88.2.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Foe V. E., Wilkinson L. E., Laird C. D. Comparative organization of active transcription units in Oncopeltus fasciatus. Cell. 1976 Sep;9(1):131–146. doi: 10.1016/0092-8674(76)90059-3. [DOI] [PubMed] [Google Scholar]
  20. GALL J. G., CALLAN H. G. H3 uridine incorporation in lampbrush chromosomes. Proc Natl Acad Sci U S A. 1962 Apr 15;48:562–570. doi: 10.1073/pnas.48.4.562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Glover C. V., Vavra K. J., Guttman S. D., Gorovsky M. A. Heat shock and deciliation induce phosphorylation of histone H1 in T. pyriformis. Cell. 1981 Jan;23(1):73–77. doi: 10.1016/0092-8674(81)90271-3. [DOI] [PubMed] [Google Scholar]
  22. Holland C. A., Mayrand S., Pederson T. Sequence complexity of nuclear and messenger RNA in HeLa cells. J Mol Biol. 1980 Apr 25;138(4):755–778. doi: 10.1016/0022-2836(80)90064-9. [DOI] [PubMed] [Google Scholar]
  23. Holmgren R., Corces V., Morimoto R., Blackman R., Meselson M. Sequence homologies in the 5' regions of four Drosophila heat-shock genes. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3775–3778. doi: 10.1073/pnas.78.6.3775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Holmgren R., Livak K., Morimoto R., Freund R., Meselson M. Studies of cloned sequences from four Drosophila heat shock loci. Cell. 1979 Dec;18(4):1359–1370. doi: 10.1016/0092-8674(79)90246-0. [DOI] [PubMed] [Google Scholar]
  25. IZAWA M., ALLEFREY V. G., MIRSKY A. E. The relationship between RNA synthesis and loop structure in lampbrush chromosomes. Proc Natl Acad Sci U S A. 1963 Apr;49:544–551. doi: 10.1073/pnas.49.4.544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Karn J., Vidali G., Boffa L. C., Allfrey V. G. Characterization of the non-histone nuclear proteins associated with rapidly labeled heterogeneous nuclear RNA. J Biol Chem. 1977 Oct 25;252(20):7307–7322. [PubMed] [Google Scholar]
  27. Kish V. M., Pederson T. Heterogeneous nuclear RNA secondary structure: oligo (U) sequences base-paired with poly (A) and their possible role as binding sites for heterogeneous nuclear RNA-specific proteins. Proc Natl Acad Sci U S A. 1977 Apr;74(4):1426–1430. doi: 10.1073/pnas.74.4.1426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kish V. M., Pederson T. Isolation and characterization of ribonucleoprotein particles containing heterogeneous nuclear RNA. Methods Cell Biol. 1978;17:377–399. doi: 10.1016/s0091-679x(08)61155-3. [DOI] [PubMed] [Google Scholar]
  29. Kish V. M., Pederson T. Ribonucleoprotein organization of polyadenylate sequences in HeLa cell heterogeneous nuclear RNA. J Mol Biol. 1975 Jun 25;95(2):227–238. doi: 10.1016/0022-2836(75)90392-7. [DOI] [PubMed] [Google Scholar]
  30. Krichevskaya A. A., Georgiev G. P. Further studies on the protein moiety in nuclear DNA-like RNA containing complexes. Biochim Biophys Acta. 1969 Dec 23;194(2):619–621. doi: 10.1016/0005-2795(69)90129-9. [DOI] [PubMed] [Google Scholar]
  31. Krüger C., Benecke B. J. In vitro translation of Drosophila heat-shock and non--heat-shock mRNAs in heterologous and homologous cell-free systems. Cell. 1981 Feb;23(2):595–603. doi: 10.1016/0092-8674(81)90155-0. [DOI] [PubMed] [Google Scholar]
  32. Kumar A., Pederson T. Comparison of proteins bound to heterogeneous nuclear RNA and messenger RNA in HeLa cells. J Mol Biol. 1975 Aug 15;96(3):353–365. doi: 10.1016/0022-2836(75)90165-5. [DOI] [PubMed] [Google Scholar]
  33. Laird C. D., Chooi W. Y. Morphology of transcription units in Drosophila melanogaster. Chromosoma. 1976 Oct 28;58(2):193–218. doi: 10.1007/BF00701359. [DOI] [PubMed] [Google Scholar]
  34. Laird C. D., Wilkinson L. E., Foe V. E., Chooi W. Y. Analysis of chromatin-associated fiber arrays. Chromosoma. 1976 Oct 28;58(2):169–190. doi: 10.1007/BF00701357. [DOI] [PubMed] [Google Scholar]
  35. Lengyel J. A., Ransom L. J., Graham M. L., Pardue M. L. Transcription and metabolism of RNA from the Drosophila melanogaster heat shock puff site 93D. Chromosoma. 1980;80(3):237–252. doi: 10.1007/BF00292683. [DOI] [PubMed] [Google Scholar]
  36. Lerner M. R., Boyle J. A., Mount S. M., Wolin S. L., Steitz J. A. Are snRNPs involved in splicing? Nature. 1980 Jan 10;283(5743):220–224. doi: 10.1038/283220a0. [DOI] [PubMed] [Google Scholar]
  37. Lifton R. P., Goldberg M. L., Karp R. W., Hogness D. S. The organization of the histone genes in Drosophila melanogaster: functional and evolutionary implications. Cold Spring Harb Symp Quant Biol. 1978;42(Pt 2):1047–1051. doi: 10.1101/sqb.1978.042.01.105. [DOI] [PubMed] [Google Scholar]
  38. Lindquist S. Regulation of protein synthesis during heat shock. Nature. 1981 Sep 24;293(5830):311–314. doi: 10.1038/293311a0. [DOI] [PubMed] [Google Scholar]
  39. Lindquist S. Varying patterns of protein synthesis in Drosophila during heat shock: implications for regulation. Dev Biol. 1980 Jun 15;77(2):463–479. doi: 10.1016/0012-1606(80)90488-1. [DOI] [PubMed] [Google Scholar]
  40. Malcolm D. B., Sommerville J. The structure of chromosome-derived ribonucleoprotein in oocytes of Triturus cristatus carnifex (Laurenti). Chromosoma. 1974;48(2):137–158. doi: 10.1007/BF00283960. [DOI] [PubMed] [Google Scholar]
  41. Martin T., Billings P., Levey A., Ozarslan S., Quinlan T., Swift H., Urbas L. Some properties of RNA:protein complexes from the nucleus of eukaryotic cells. Cold Spring Harb Symp Quant Biol. 1974;38:921–932. doi: 10.1101/sqb.1974.038.01.094. [DOI] [PubMed] [Google Scholar]
  42. Maxwell I. H., Maxwell F., Hahn W. E. General occurrence and transcription of intervening sequences in mouse genes expressed via polyadenylated mRNA. Nucleic Acids Res. 1980 Dec 11;8(23):5875–5894. doi: 10.1093/nar/8.23.5875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Mayrand S., Pederson T. Heat shock alters nuclear ribonucleoprotein assembly in Drosophila cells. Mol Cell Biol. 1983 Feb;3(2):161–171. doi: 10.1128/mcb.3.2.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Mayrand S., Pederson T. Nuclear ribonucleoprotein particles probed in living cells. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2208–2212. doi: 10.1073/pnas.78.4.2208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. McKenzie S. L., Meselson M. Translation in vitro of Drosophila heat-shock messages. J Mol Biol. 1977 Nov 25;117(1):279–283. doi: 10.1016/0022-2836(77)90035-3. [DOI] [PubMed] [Google Scholar]
  46. McKnight S. L., Miller O. L., Jr Post-replicative nonribosomal transcription units in D. melanogaster embryos. Cell. 1979 Jul;17(3):551–563. doi: 10.1016/0092-8674(79)90263-0. [DOI] [PubMed] [Google Scholar]
  47. McKnight S. L., Miller O. L., Jr Ultrastructural patterns of RNA synthesis during early embryogenesis of Drosophila melanogaster. Cell. 1976 Jun;8(2):305–319. doi: 10.1016/0092-8674(76)90014-3. [DOI] [PubMed] [Google Scholar]
  48. Miller O. L., Jr, Bakken A. H. Morphological studies of transcription. Acta Endocrinol Suppl (Copenh) 1972;168:155–177. doi: 10.1530/acta.0.071s155. [DOI] [PubMed] [Google Scholar]
  49. Monneron A., Bernhard W. Fine structural organization of the interphase nucleus in some mammalian cells. J Ultrastruct Res. 1969 May;27(3):266–288. doi: 10.1016/s0022-5320(69)80017-1. [DOI] [PubMed] [Google Scholar]
  50. Mount S. M., Pettersson I., Hinterberger M., Karmas A., Steitz J. A. The U1 small nuclear RNA-protein complex selectively binds a 5' splice site in vitro. Cell. 1983 Jun;33(2):509–518. doi: 10.1016/0092-8674(83)90432-4. [DOI] [PubMed] [Google Scholar]
  51. Mount S. M. RNA processing. Sequences that signal where to splice. 1983 Jul 28-Aug 3Nature. 304(5924):309–310. doi: 10.1038/304309a0. [DOI] [PubMed] [Google Scholar]
  52. Munroe S. H. Ribonucleoprotein structure of adenovirus nuclear RNA probed by nuclease digestion. J Mol Biol. 1982 Dec 15;162(3):585–606. doi: 10.1016/0022-2836(82)90390-4. [DOI] [PubMed] [Google Scholar]
  53. Nevins J. R., Darnell J. E., Jr Steps in the processing of Ad2 mRNA: poly(A)+ nuclear sequences are conserved and poly(A) addition precedes splicing. Cell. 1978 Dec;15(4):1477–1493. doi: 10.1016/0092-8674(78)90071-5. [DOI] [PubMed] [Google Scholar]
  54. Niessing J., Sekeris C. E. Further studies on nuclear ribonucleoprotein particles containing DNA-like RNA from rat liver. Biochim Biophys Acta. 1971 Oct;247(3):391–403. doi: 10.1016/0005-2787(71)90024-4. [DOI] [PubMed] [Google Scholar]
  55. Nowak L., Marvil D. K., Thomas J. O., Boublik M., Szer W. A single-stranded nucleic acid-binding protein from Artemia salina. II. Interaction with nucleic acids. J Biol Chem. 1980 Jul 10;255(13):6473–6478. [PubMed] [Google Scholar]
  56. Ohlendorf D. H., Anderson W. F., Fisher R. G., Takeda Y., Matthews B. W. The molecular basis of DNA-protein recognition inferred from the structure of cro repressor. Nature. 1982 Aug 19;298(5876):718–723. doi: 10.1038/298718a0. [DOI] [PubMed] [Google Scholar]
  57. Ohlsson R. I., van Eekelen C., Philipson L. Non-random localization of ribonucleoprotein (RNP) structures within an adenovirus mRNA precursor. Nucleic Acids Res. 1982 May 25;10(10):3053–3068. doi: 10.1093/nar/10.10.3053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. PETRALLI J. K., MERIGAN T. C., WILBUR J. R. CIRCULATING INTERFERON AFTER MEASLES VACCINATION. N Engl J Med. 1965 Jul 22;273:198–201. doi: 10.1056/NEJM196507222730405. [DOI] [PubMed] [Google Scholar]
  59. Pederson T. Chromatin structure and gene transcription: nucleosomes permit a new synthesis. Int Rev Cytol. 1978;55:1–21. doi: 10.1016/s0074-7696(08)61884-7. [DOI] [PubMed] [Google Scholar]
  60. Pederson T., Davis N. G. Messenger RNA processing and nuclear structure: isolation of nuclear ribonucleoprotein particles containing beta-globin messenger RNA precursors. J Cell Biol. 1980 Oct;87(1):47–54. doi: 10.1083/jcb.87.1.47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Pederson T. Messenger RNA biosynthesis and nuclear structure. Am Sci. 1981 Jan-Feb;69(1):76–84. [PubMed] [Google Scholar]
  62. Pederson T., Munroe S. H. Ribonucleoprotein organization of eukaryotic RNA. XV. Different nucleoprotein structures of globin messenger RNA sequences in nuclear and polyribosomal ribonucleoprotein particles. J Mol Biol. 1981 Aug 25;150(4):509–524. doi: 10.1016/0022-2836(81)90377-6. [DOI] [PubMed] [Google Scholar]
  63. Pederson T. Proteins associated with heterogeneous nuclear RNA in eukaryotic cells. J Mol Biol. 1974 Feb 25;83(2):163–183. doi: 10.1016/0022-2836(74)90386-6. [DOI] [PubMed] [Google Scholar]
  64. Preobrazhensky A. A., Spirin A. S. Informosomes and their protein components: the present state of knowledge. Prog Nucleic Acid Res Mol Biol. 1978;21:1–38. doi: 10.1016/s0079-6603(08)60265-2. [DOI] [PubMed] [Google Scholar]
  65. Pullman J. M., Martin T. E. Reconstitution of nucleoprotein complexes with mammalian heterogeneous nuclear ribonucleoprotein (hnRNP) core proteins. J Cell Biol. 1983 Jul;97(1):99–111. doi: 10.1083/jcb.97.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. RUIZ-GOMEZ J., ISAACS A. Interferon production by different viruses. Virology. 1963 Jan;19:8–12. doi: 10.1016/0042-6822(63)90018-7. [DOI] [PubMed] [Google Scholar]
  67. Rogers J., Wall R. A mechanism for RNA splicing. Proc Natl Acad Sci U S A. 1980 Apr;77(4):1877–1879. doi: 10.1073/pnas.77.4.1877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Spradling A., Pardue M. L., Penman S. Messenger RNA in heat-shocked Drosophila cells. J Mol Biol. 1977 Feb 5;109(4):559–587. doi: 10.1016/s0022-2836(77)80091-0. [DOI] [PubMed] [Google Scholar]
  69. Spradling A., Penman S., Pardue M. L. Analysis of drosophila mRNA by in situ hybridization: sequences transcribed in normal and heat shocked cultured cells. Cell. 1975 Apr;4(4):395–404. doi: 10.1016/0092-8674(75)90160-9. [DOI] [PubMed] [Google Scholar]
  70. Steitz J. A., Kamen R. Arrangement of 30S heterogeneous nuclear ribonucleoprotein on polyoma virus late nuclear transcripts. Mol Cell Biol. 1981 Jan;1(1):21–34. doi: 10.1128/mcb.1.1.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Stevens B. J., Swift H. RNA transport from nucleus to cytoplasm in Chironomus salivary glands. J Cell Biol. 1966 Oct;31(1):55–77. doi: 10.1083/jcb.31.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Storti R. V., Scott M. P., Rich A., Pardue M. L. Translational control of protein synthesis in response to heat shock in D. melanogaster cells. Cell. 1980 Dec;22(3):825–834. doi: 10.1016/0092-8674(80)90559-0. [DOI] [PubMed] [Google Scholar]
  73. Stévenin J., Gattoni R., Keohavong P., Jacob M. Mild nuclease treatment as a probe for a non-random distribution of adenovirus-specific RNA sequences and of cellular RNA in nuclear ribonucleoprotein fibrils. J Mol Biol. 1982 Mar 5;155(3):185–205. doi: 10.1016/0022-2836(82)90001-8. [DOI] [PubMed] [Google Scholar]
  74. Stévenin J., Jacob M. Effects of sodium chloride and pancreatic ribonuclease on the rat-brain nuclear particles: the fate of the protein moiety. Eur J Biochem. 1974 Aug 15;47(1):129–137. doi: 10.1111/j.1432-1033.1974.tb03676.x. [DOI] [PubMed] [Google Scholar]
  75. Tissières A., Mitchell H. K., Tracy U. M. Protein synthesis in salivary glands of Drosophila melanogaster: relation to chromosome puffs. J Mol Biol. 1974 Apr 15;84(3):389–398. doi: 10.1016/0022-2836(74)90447-1. [DOI] [PubMed] [Google Scholar]
  76. Tsanev R. G., Djondjurov L. P. Ultrastructure of free ribonucleoprotein complexes in spread mammalian nuclei. J Cell Biol. 1982 Sep;94(3):662–666. doi: 10.1083/jcb.94.3.662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Wieben E. D., Pederson T. Small nuclear ribonucleoproteins of Drosophila: identification of U1 RNA-associated proteins and their behavior during heat shock. Mol Cell Biol. 1982 Aug;2(8):914–920. doi: 10.1128/mcb.2.8.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Winter R. B., Berg O. G., von Hippel P. H. Diffusion-driven mechanisms of protein translocation on nucleic acids. 3. The Escherichia coli lac repressor--operator interaction: kinetic measurements and conclusions. Biochemistry. 1981 Nov 24;20(24):6961–6977. doi: 10.1021/bi00527a030. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES